Spectroscopic Analysis of Peptide Aggregation

The self-assembly of molecules into aggregates has a profound effect on the chemical activity of those molecules.  The self-assembly of peptides provides several examples of this phenomenon.  In normal, healthy systems peptide self-assembly is essential to the formation of muscle (myosin fragments) and the cytoskeleton of cells (actin filaments).  In abnormal, diseased systems peptide self-assembly is an early step in the formation of aggregates that deposit in cells, e.g., Alzheimer’s Disease and Huntington’s Disease.  The aggregation of peptides into an insoluble inclusion body state is also a serious problem for biotechnology and biomedical research.  Moreover, peptide self-assembly into aggregates can have a profound effect on the processing and effectiveness of therapeutic peptides.  The particular cases of insulin and residues 7 - 37 of glucagon-like peptide-1 (GLP-1(7-37)) are of special interest because of their role in the treatment of diabetes.

The purpose of this research is to determine details of the mechanism of the self-assembly and aggregation of insulin and GLP-1 (7-37).  Any attempt to elucidate details of aggregation must deal—in some way—with the variety of particle sizes in a solution in which self-assembly is occurring.  The experimental method used must somehow characterize all of the individual species in the solution.  To accomplish this, the unique combination of resonance light scattering and capillary electrophoresis detected by laser light scattering will be used.